Microfluidics is a rapidly emerging field of interest. It is defined by the manipulation of fluids, typically aqueous solutions, on the scales of microliters. Microfluidic chips, miniaturized systems which control fluid flow, and processing, can be used for a variety of applications. These applications are typically in the realm of biochemistry—drug screening, stem cell analysis, cell sorting, and disease detection. Advantages of a microfluidic approach to these applications include reduced reagent volume, the ability to parallel process many samples on a small chip, and an overall reduction in system scale, allowing for field-portable instruments.
Microfluidic chips are systems of small channels (usually 10-100 microns in size), often with integrated pumps and mixing chambers, and occasionally ports for electrical or optical analysis. Much of the worth of these chips lies in the fact that they are built with techniques amenable to batch fabrication. As in the semiconductor chip industry, batch fabrication enables lower cost production, and increased integration of functionality on a single chip. There are a wide variety of batch fabrication techniques capable of producing microfluidic chips—etching channels in glass or silicon, injection molding of plastics, replication molding of PDMS (polydimethylsiloxane) polymer. More recently, there has been interest in adapting printed circuit board (PCB) techniques to create microfluidic systems.
Printed circuit board fabrication techniques are a natural fit to the problem of creating microfluidic chips. The size scales involved (50-100 micron traces) are the same size scales used in microfluidic chips for channels; the fabrication technologies have been well-developed by the electronics industry over the past 40 years, with associated reduction of production cost; finally, these techniques allow for easy integration of electronic systems with microfluidic ones.
PCBs are composed of alternating planar layers of insulating materials (FR4, polyimide, ceramics), and layers of conducting metals (copper, aluminum, gold) which have been defined through photolithography to form systems of traces, or conducting circuits. Holes between layers are drilled, and sometimes plated, to allow for vias, or vertical connections between layers.
The most common materials system for a PCB is one composed of FR4 (fiberglass in an epoxy matrix) for the insulator and copper for the traces. Boards are typically fabricated by performing photolithography and etching on a two-sided copper-clad FR4 core, drilling and plating holes for buried vias, and then laminating these cores together. By doing so, finished boards with an arbitrary number of buried traces and vias may be produced. Finally, holes for discrete components (semiconductor devices, resistors, etc) are drilled and plated, as are alignment and mounting holes. Boards are typically processed in the form of large panels, and later sawed (diced) into individual boards, allowing many discrete boards to be fabricated in a single batch.
A variety of implementations of PCB technology to microfluidic applications have been tried, all of which require either modification of the PCB process flow, or some type of post-processing to obtain a microfluidic system. These include:                1. Etching a top copper layer to form a 3-sided channel (FR4 bottom, copper sidewalls) and then sealing the channel with a plate to form a fully enclosed channel. (Merkel, Graeber, Pagel, 1999; Nguyen and Huang, 2000). This technique can create microfluidic chips with two layers.        2. Etching a top copper layer on both of two PCBs, which are then aligned and laminated to form a fully enclosed system of channels (Wego, Richter, Pagel, 2001). This technique can be extended to an arbitrary number of microfluidic channel layers.        3. A modification of technique (1), using a thin silicone membrane instead of a plate to seal 3-sided channels (Läritz, Pagel, 2000)        4. Laminating a PCB with “pre-carved channels” to another PCB (Lian, O'Rourke, et. al., 2009)        5. Etching a 3-sided channel into a polyimide layer, and then sealing the resulting open channel with a film of polyimide (Metz, Holzer, Renaud, 2001)        
All of these techniques rely on fabricating a system of open (3-sided) channels, and then laminating them with either a cover plate/film, or to another PCB. While much of the process flow is compatible with widespread industry practices, there is often a process step inserted into this process flow. Additionally, care must be taken during lamination steps that the open channels do not become filled with laminating resin, and thus blocked.
Microfluidic chips fabricated out of polydimethylsiloxane (PDMS) are a field that rapidly expanded in the early 2000's. PDMS is a type of silicone polymer that is: biocompatible (useful as a container for a variety of biochemical reactions); optically transparent, with low autofluorescence (good for optical monitoring of biochemical reactions); and mechanically, quite soft. The fact that it is deformable makes it an excellent gasket material, and allows for the construction of integrated microfluidic channels (“Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane)”, David C. Duffy, J. Cooper McDonald, Olivier J. A. Schueller, and George M. Whitesides, Analytical Chemistry, 1998, 70, 4974-4984) and valves (“Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography”, Marc A. Unger, Hou-Pu Chou, Todd Thorsen, Axel Scherer, Stephen R. Quake, Science, Vol 288 7 Apr. 2000 p. 113-116), through replication molding. PDMS is inexpensive, and the ease with which it can be used to create large, integrated microfluidic systems has enabled its widespread use.
Unfortunately, connecting PDMS microfluidic chips to other control or analysis systems is often difficult. The most common approach used is to punch cylindrical hole through the chip which intersects one of the fluid channels; a stainless steel capillary tube, which will later be connected to a small diameter Tygon® tube, is then inserted in the hole, and kept in place by the gasket-like deformation of the PDMS. This process must be repeated for each channel in the chip which requires access to outside fluids or controls (each port). This is a labor intensive, and generally painful process. Finally, due to the mismatch in size scales between the connecting tubes, and the channels on the chip, the chip may have to be much larger in area than required by its functionality to accommodate the connections. This problem is very similar to that faced by semiconductor chip designers, who must allocate large amounts of chip area to wire bonding/bump bonding pads for connection to the chip package.
Another approach to connection is to machine a manifold structure having on one side a flat face (output face), which will be pressed to the PDMS chip, and on the other, capillary tubes which will be connected to tubing. The manifold contains routing channels from the tubes to small holes on the output face, which match up to channels on the PDMS chip. Such manifolds have been manufactured through techniques such as injection molding and conventional metal machining (milling, electro-discharge machining, etc) techniques. A connection manifold is directly analogous to a socket for integrated circuits in functionality.